IL248948B - - α3hydroxy--β3-methoxymethyl-5)-21-methyl-2h-tetrazole-2-yl-19-nor-α5-paragnane-20-one and its pharmaceutical preparation - Google Patents

Info

Publication number

IL248948B

IL248948B IL248948A IL24894816A IL248948B IL 248948 B IL248948 B IL 248948B IL 248948 A IL248948 A IL 248948A IL 24894816 A IL24894816 A IL 24894816A IL 248948 B IL248948 B IL 248948B

Authority

IL

Israel

Prior art keywords

mmol

compound

solution

added

synthesis

Prior art date

2014-05-29

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• 239000008194 pharmaceutical composition Substances 0.000 title claims description 7
• 150000001875 compounds Chemical class 0.000 claims description 363
• 125000000217 alkyl group Chemical group 0.000 claims description 220
• 230000015572 biosynthetic process Effects 0.000 claims description 185
• 238000003786 synthesis reaction Methods 0.000 claims description 182
• 239000000203 mixture Substances 0.000 claims description 177
• 125000004432 carbon atom Chemical group C* 0.000 claims description 176
• 125000005842 heteroatom Chemical group 0.000 claims description 159
• 125000000623 heterocyclic group Chemical group 0.000 claims description 149
• 125000003118 aryl group Chemical group 0.000 claims description 143
• 125000000304 alkynyl group Chemical group 0.000 claims description 118
• 125000003342 alkenyl group Chemical group 0.000 claims description 117
• -1 3–pentanyl Chemical group 0.000 claims description 110
• 125000004452 carbocyclyl group Chemical group 0.000 claims description 96
• 125000001072 heteroaryl group Chemical group 0.000 claims description 83
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 69
• 125000001424 substituent group Chemical group 0.000 claims description 69
• 238000006243 chemical reaction Methods 0.000 claims description 68
• 229910052739 hydrogen Inorganic materials 0.000 claims description 49
• 229910052799 carbon Inorganic materials 0.000 claims description 46
• 229910052760 oxygen Inorganic materials 0.000 claims description 45
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 44
• 150000003254 radicals Chemical class 0.000 claims description 44
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 42
• 229910052757 nitrogen Inorganic materials 0.000 claims description 42
• 229920006395 saturated elastomer Polymers 0.000 claims description 42
• 229910052717 sulfur Inorganic materials 0.000 claims description 41
• 239000012071 phase Substances 0.000 claims description 38
• 125000001313 C5-C10 heteroaryl group Chemical group 0.000 claims description 37
• 125000004404 heteroalkyl group Chemical group 0.000 claims description 37
• 239000001257 hydrogen Substances 0.000 claims description 36
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 33
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 33
• 239000001301 oxygen Substances 0.000 claims description 33
• 239000011593 sulfur Substances 0.000 claims description 31
• 125000003545 alkoxy group Chemical group 0.000 claims description 26
• QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 26
• 150000002431 hydrogen Chemical class 0.000 claims description 22
• 125000004209 (C1-C8) alkyl group Chemical group 0.000 claims description 21
• 238000000034 method Methods 0.000 claims description 21
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 20
• 125000004122 cyclic group Chemical group 0.000 claims description 20
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 19
• 125000004450 alkenylene group Chemical group 0.000 claims description 18
• 125000002947 alkylene group Chemical group 0.000 claims description 18
• 239000011203 carbon fibre reinforced carbon Substances 0.000 claims description 18
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 18
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• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 15
• 229960003692 gamma aminobutyric acid Drugs 0.000 claims description 15
• BTCSSZJGUNDROE-UHFFFAOYSA-N gamma-aminobutyric acid Chemical compound NCCCC(O)=O BTCSSZJGUNDROE-UHFFFAOYSA-N 0.000 claims description 15
• 125000003710 aryl alkyl group Chemical group 0.000 claims description 14
• 150000001721 carbon Chemical group 0.000 claims description 14
• 210000004027 cell Anatomy 0.000 claims description 14
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 14
• 229910052796 boron Inorganic materials 0.000 claims description 13
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 13
• 125000004433 nitrogen atom Chemical group N* 0.000 claims description 13
• 206010010904 Convulsion Diseases 0.000 claims description 12
• 125000002252 acyl group Chemical group 0.000 claims description 12
• 125000000392 cycloalkenyl group Chemical group 0.000 claims description 12
• 125000001188 haloalkyl group Chemical group 0.000 claims description 12
• 150000003431 steroids Chemical class 0.000 claims description 12
• 238000011282 treatment Methods 0.000 claims description 12
• 125000004765 (C1-C4) haloalkyl group Chemical group 0.000 claims description 11
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 11
• 238000004128 high performance liquid chromatography Methods 0.000 claims description 11
• 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 10
• 125000006708 (C5-C14) heteroaryl group Chemical group 0.000 claims description 10
• 125000006163 5-membered heteroaryl group Chemical group 0.000 claims description 10
• 201000009916 Postpartum depression Diseases 0.000 claims description 10
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 10
• ZOXJGFHDIHLPTG-UHFFFAOYSA-N Boron Chemical compound [B] ZOXJGFHDIHLPTG-UHFFFAOYSA-N 0.000 claims description 9
• OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 claims description 9
• XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 claims description 9
• 125000002619 bicyclic group Chemical group 0.000 claims description 9
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• 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 claims description 9
• 125000002950 monocyclic group Chemical group 0.000 claims description 9
• 229910052698 phosphorus Inorganic materials 0.000 claims description 9
• 239000011574 phosphorus Substances 0.000 claims description 9
• 150000003839 salts Chemical class 0.000 claims description 9
• 229910052710 silicon Inorganic materials 0.000 claims description 9
• 239000010703 silicon Substances 0.000 claims description 9
• 208000024891 symptom Diseases 0.000 claims description 9
• 125000002853 C1-C4 hydroxyalkyl group Chemical group 0.000 claims description 8
• VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 claims description 8
• 239000005977 Ethylene Substances 0.000 claims description 8
• 125000004442 acylamino group Chemical group 0.000 claims description 8
• 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 8
• 208000035475 disorder Diseases 0.000 claims description 8
• 229910052736 halogen Inorganic materials 0.000 claims description 8
• 150000002367 halogens Chemical class 0.000 claims description 8
• 125000004446 heteroarylalkyl group Chemical group 0.000 claims description 8
• 125000000008 (C1-C10) alkyl group Chemical group 0.000 claims description 7
• 125000004429 atom Chemical group 0.000 claims description 7
• 206010015037 epilepsy Diseases 0.000 claims description 7
• 230000002829 reductive effect Effects 0.000 claims description 7
• 125000006714 (C3-C10) heterocyclyl group Chemical group 0.000 claims description 6
• 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 claims description 6
• YBYIRNPNPLQARY-UHFFFAOYSA-N 1H-indene Chemical compound C1=CC=C2CC=CC2=C1 YBYIRNPNPLQARY-UHFFFAOYSA-N 0.000 claims description 6
• UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 6
• 125000003282 alkyl amino group Chemical group 0.000 claims description 6
• 125000003368 amide group Chemical group 0.000 claims description 6
• 125000001769 aryl amino group Chemical group 0.000 claims description 6
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 6
• GVEPBJHOBDJJJI-UHFFFAOYSA-N fluoranthene Chemical compound C1=CC(C2=CC=CC=C22)=C3C2=CC=CC3=C1 GVEPBJHOBDJJJI-UHFFFAOYSA-N 0.000 claims description 6
• 125000004474 heteroalkylene group Chemical group 0.000 claims description 6
• 125000004475 heteroaralkyl group Chemical group 0.000 claims description 6
• 150000002430 hydrocarbons Chemical group 0.000 claims description 6
• 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 6
• 210000002569 neuron Anatomy 0.000 claims description 6
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 6
• 125000006574 non-aromatic ring group Chemical group 0.000 claims description 6
• QQONPFPTGQHPMA-UHFFFAOYSA-N propylene Natural products CC=C QQONPFPTGQHPMA-UHFFFAOYSA-N 0.000 claims description 6
• 125000004805 propylene group Chemical group [H]C([H])([H])C([H])([*:1])C([H])([H])[*:2] 0.000 claims description 6
• 125000000547 substituted alkyl group Chemical group 0.000 claims description 6
• 125000003107 substituted aryl group Chemical group 0.000 claims description 6
• 125000006164 6-membered heteroaryl group Chemical group 0.000 claims description 5
• 125000006374 C2-C10 alkenyl group Chemical group 0.000 claims description 5
• 206010039897 Sedation Diseases 0.000 claims description 5
• 125000003277 amino group Chemical group 0.000 claims description 5
• 230000027455 binding Effects 0.000 claims description 5
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 5
• 239000003814 drug Substances 0.000 claims description 5
• 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 5
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 5
• 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 5
• 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 5
• 125000001624 naphthyl group Chemical group 0.000 claims description 5
• 125000006239 protecting group Chemical group 0.000 claims description 5
• 230000036280 sedation Effects 0.000 claims description 5
• 239000000126 substance Substances 0.000 claims description 5
• 125000006650 (C2-C4) alkynyl group Chemical group 0.000 claims description 4
• 125000006376 (C3-C10) cycloalkyl group Chemical group 0.000 claims description 4
• 125000004973 1-butenyl group Chemical group C(=CCC)* 0.000 claims description 4
• 125000004972 1-butynyl group Chemical group [H]C([H])([H])C([H])([H])C#C* 0.000 claims description 4
• 125000004974 2-butenyl group Chemical group C(C=CC)* 0.000 claims description 4
• 125000000069 2-butynyl group Chemical group [H]C([H])([H])C#CC([H])([H])* 0.000 claims description 4
• 102000005915 GABA Receptors Human genes 0.000 claims description 4
• 108010005551 GABA Receptors Proteins 0.000 claims description 4
• 241001465754 Metazoa Species 0.000 claims description 4
• UFWIBTONFRDIAS-UHFFFAOYSA-N Naphthalene Chemical compound C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 claims description 4
• GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims description 4
• RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical group C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 4
• 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 4
• 125000004423 acyloxy group Chemical group 0.000 claims description 4
• 125000004947 alkyl aryl amino group Chemical group 0.000 claims description 4
• HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 claims description 4
• MWPLVEDNUUSJAV-UHFFFAOYSA-N anthracene Chemical compound C1=CC=CC2=CC3=CC=CC=C3C=C21 MWPLVEDNUUSJAV-UHFFFAOYSA-N 0.000 claims description 4
• HONIICLYMWZJFZ-UHFFFAOYSA-N azetidine Chemical compound C1CNC1 HONIICLYMWZJFZ-UHFFFAOYSA-N 0.000 claims description 4
• 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 claims description 4
• CUFNKYGDVFVPHO-UHFFFAOYSA-N azulene Chemical compound C1=CC=CC2=CC=CC2=C1 CUFNKYGDVFVPHO-UHFFFAOYSA-N 0.000 claims description 4
• 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 4
• CREMABGTGYGIQB-UHFFFAOYSA-N carbon carbon Chemical compound C.C CREMABGTGYGIQB-UHFFFAOYSA-N 0.000 claims description 4
• WDECIBYCCFPHNR-UHFFFAOYSA-N chrysene Chemical compound C1=CC=CC2=CC=C3C4=CC=CC=C4C=CC3=C21 WDECIBYCCFPHNR-UHFFFAOYSA-N 0.000 claims description 4
• VPUGDVKSAQVFFS-UHFFFAOYSA-N coronene Chemical compound C1=C(C2=C34)C=CC3=CC=C(C=C3)C4=C4C3=CC=C(C=C3)C4=C2C3=C1 VPUGDVKSAQVFFS-UHFFFAOYSA-N 0.000 claims description 4
• 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 4
• 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 4
• 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 4
• 125000000596 cyclohexenyl group Chemical group C1(=CCCCC1)* 0.000 claims description 4
• 125000006639 cyclohexyl carbonyl group Chemical group 0.000 claims description 4
• 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 4
• 125000000640 cyclooctyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 4
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• 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 4
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• BBEAQIROQSPTKN-UHFFFAOYSA-N pyrene Chemical compound C1=CC=C2C=CC3=CC=CC4=CC=C1C2=C43 BBEAQIROQSPTKN-UHFFFAOYSA-N 0.000 claims description 4
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• 125000006704 (C5-C6) cycloalkyl group Chemical group 0.000 claims description 3
• GVNVAWHJIKLAGL-UHFFFAOYSA-N 2-(cyclohexen-1-yl)cyclohexan-1-one Chemical compound O=C1CCCCC1C1=CCCCC1 GVNVAWHJIKLAGL-UHFFFAOYSA-N 0.000 claims description 3
• HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 claims description 3
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• 125000000530 1-propynyl group Chemical group [H]C([H])([H])C#C* 0.000 claims description 2
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• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 claims 148
• 239000012267 brine Substances 0.000 claims 147
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims 144
• HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 claims 140
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims 129
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• 238000005481 NMR spectroscopy Methods 0.000 claims 96
• 239000012044 organic layer Substances 0.000 claims 77
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 claims 72
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims 71
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims 66
• 239000012043 crude product Substances 0.000 claims 61
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• 238000004895 liquid chromatography mass spectrometry Methods 0.000 claims 58
• 239000000047 product Substances 0.000 claims 48
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• 208000005809 status epilepticus Diseases 0.000 claims 43
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 claims 38
• 238000002953 preparative HPLC Methods 0.000 claims 38
• 229910052938 sodium sulfate Inorganic materials 0.000 claims 38
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• 229910052943 magnesium sulfate Inorganic materials 0.000 claims 36
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• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims 34
• 239000000376 reactant Substances 0.000 claims 33
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• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims 26
• 238000003818 flash chromatography Methods 0.000 claims 23
• LEHBURLTIWGHEM-UHFFFAOYSA-N pyridinium chlorochromate Chemical compound [O-][Cr](Cl)(=O)=O.C1=CC=[NH+]C=C1 LEHBURLTIWGHEM-UHFFFAOYSA-N 0.000 claims 22
• 229910052794 bromium Inorganic materials 0.000 claims 21
• 125000001475 halogen functional group Chemical group 0.000 claims 21
• WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims 18
• GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims 18
• 239000000543 intermediate Substances 0.000 claims 18
• RCBVKBFIWMOMHF-UHFFFAOYSA-L hydroxy-(hydroxy(dioxo)chromio)oxy-dioxochromium;pyridine Chemical compound C1=CC=NC=C1.C1=CC=NC=C1.O[Cr](=O)(=O)O[Cr](O)(=O)=O RCBVKBFIWMOMHF-UHFFFAOYSA-L 0.000 claims 16
• 239000000284 extract Substances 0.000 claims 15
• 239000010410 layer Substances 0.000 claims 14
• LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 claims 14
• CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 claims 13
• QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims 12
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims 12
• 238000010898 silica gel chromatography Methods 0.000 claims 12
• 239000007858 starting material Substances 0.000 claims 12
• JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 claims 12
• 239000005457 ice water Substances 0.000 claims 11
• 239000002904 solvent Substances 0.000 claims 11
• QWENRTYMTSOGBR-UHFFFAOYSA-N 1H-1,2,3-Triazole Chemical compound C=1C=NNN=1 QWENRTYMTSOGBR-UHFFFAOYSA-N 0.000 claims 10
• 239000011734 sodium Substances 0.000 claims 10
• XZGLNCKSNVGDNX-UHFFFAOYSA-N 5-methyl-2h-tetrazole Chemical compound CC=1N=NNN=1 XZGLNCKSNVGDNX-UHFFFAOYSA-N 0.000 claims 9
• DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 claims 9
• 239000006227 byproduct Substances 0.000 claims 9
• JHYNXXDQQHTCHJ-UHFFFAOYSA-M ethyl(triphenyl)phosphanium;bromide Chemical compound [Br-].C=1C=CC=CC=1[P+](C=1C=CC=CC=1)(CC)C1=CC=CC=C1 JHYNXXDQQHTCHJ-UHFFFAOYSA-M 0.000 claims 9
• 125000004438 haloalkoxy group Chemical group 0.000 claims 9
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims 8
• 239000007864 aqueous solution Substances 0.000 claims 8
• 125000002768 hydroxyalkyl group Chemical group 0.000 claims 8
• 229910000104 sodium hydride Inorganic materials 0.000 claims 8
• BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 claims 7
• 241000699670 Mus sp. Species 0.000 claims 7
• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims 7
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims 7
• UWTDFICHZKXYAC-UHFFFAOYSA-N boron;oxolane Chemical compound [B].C1CCOC1 UWTDFICHZKXYAC-UHFFFAOYSA-N 0.000 claims 7
• 239000012141 concentrate Substances 0.000 claims 7
• 239000000706 filtrate Substances 0.000 claims 7
• QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 claims 6
• WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 claims 6
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims 6
• WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 claims 6
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims 6
• INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 claims 6
• 229910052744 lithium Inorganic materials 0.000 claims 6
• 229910000027 potassium carbonate Inorganic materials 0.000 claims 6
• 239000000843 powder Substances 0.000 claims 6
• 230000028527 righting reflex Effects 0.000 claims 6
• VTBHBNXGFPTBJL-UHFFFAOYSA-N 4-tert-butyl-1-sulfanylidene-2,6,7-trioxa-1$l^{5}-phosphabicyclo[2.2.2]octane Chemical compound C1OP2(=S)OCC1(C(C)(C)C)CO2 VTBHBNXGFPTBJL-UHFFFAOYSA-N 0.000 claims 5
• NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 claims 5
• 238000006646 Dess-Martin oxidation reaction Methods 0.000 claims 5
• 241000700159 Rattus Species 0.000 claims 5
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 claims 5
• 229910021529 ammonia Inorganic materials 0.000 claims 5
• 238000003556 assay Methods 0.000 claims 5
• NKLCNNUWBJBICK-UHFFFAOYSA-N dess–martin periodinane Chemical compound C1=CC=C2I(OC(=O)C)(OC(C)=O)(OC(C)=O)OC(=O)C2=C1 NKLCNNUWBJBICK-UHFFFAOYSA-N 0.000 claims 5
• GNOIPBMMFNIUFM-UHFFFAOYSA-N hexamethylphosphoric triamide Chemical compound CN(C)P(=O)(N(C)C)N(C)C GNOIPBMMFNIUFM-UHFFFAOYSA-N 0.000 claims 5
• 239000007788 liquid Substances 0.000 claims 5
• YNESATAKKCNGOF-UHFFFAOYSA-N lithium bis(trimethylsilyl)amide Chemical compound [Li+].C[Si](C)(C)[N-][Si](C)(C)C YNESATAKKCNGOF-UHFFFAOYSA-N 0.000 claims 5
• 235000011181 potassium carbonates Nutrition 0.000 claims 5
• 238000010791 quenching Methods 0.000 claims 5
• 230000002441 reversible effect Effects 0.000 claims 5
• 238000012360 testing method Methods 0.000 claims 5
• 238000005160 1H NMR spectroscopy Methods 0.000 claims 4
• KJUGUADJHNHALS-UHFFFAOYSA-N 1H-tetrazole Chemical compound C=1N=NNN=1 KJUGUADJHNHALS-UHFFFAOYSA-N 0.000 claims 4
• 208000000103 Anorexia Nervosa Diseases 0.000 claims 4
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• NXPHGHWWQRMDIA-UHFFFAOYSA-M magnesium;carbanide;bromide Chemical compound [CH3-].[Mg+2].[Br-] NXPHGHWWQRMDIA-UHFFFAOYSA-M 0.000 claims 4
• 239000012074 organic phase Substances 0.000 claims 4
• KJIFKLIQANRMOU-UHFFFAOYSA-N oxidanium;4-methylbenzenesulfonate Chemical compound O.CC1=CC=C(S(O)(=O)=O)C=C1 KJIFKLIQANRMOU-UHFFFAOYSA-N 0.000 claims 4
• 108700023468 protein-bound SN-C polysaccharide Proteins 0.000 claims 4
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims 4
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